Traditional Chinese and western medicine combined medicine for treating tympanic membrane perforation and preparation method of traditional Chinese and western medicine combined medicine

Abstract

The invention discloses a traditional Chinese and western medicine combined medicine for treating tympanic membrane perforation and a preparation method thereof, the traditional Chinese and western medicine combined medicine comprises traditional Chinese medicine components and western medicine components, and the traditional Chinese medicine components comprise 6-30 g of safflower carthamus, 10-40 g of angelica sinensis, 6-30 g of frankincense, 6-30 g of myrrh, 6-30 g of ligusticum wallichii and 10-20 g of pollen typhae; the western medicine component is alpha-chymotrypsin, and the dosage of the alpha-chymotrypsin is 4000U per milliliter of the mixed solution. The invention belongs to the technical field of medicines, and particularly relates to a traditional Chinese and western medicine combined medicine for treating tympanic membrane perforation and a preparation method thereof.

Description

Technical Field

[0001] This invention belongs to the field of medical technology, specifically referring to a combination of traditional Chinese and Western medicine for treating tympanic membrane perforation and its preparation method. Background Technology

[0002] Tympanic membrane perforation is a common otolaryngological disease, often caused by factors such as chronic suppurative otitis media and ear trauma. Large perforations of the pars tensa of the tympanic membrane caused by chronic suppurative otitis media (perforation edge <1mm from the tympanic annulus) are particularly challenging to treat clinically. Traditional treatment methods primarily involve surgical repair, such as type I tympanoplasty. However, this type of surgery has several drawbacks: it requires the assistance of otological microscopy equipment and demands a high level of surgeon experience; patients need to be hospitalized for more than two weeks, and the treatment cost is expensive (approximately 10,000-20,000 yuan per case); postoperative complications may include facial paralysis and sensorineural hearing loss, and there is a 5%-10% risk of tympanic membrane reperforation.

[0003] Currently, both domestic and international researchers have attempted to treat small tympanic membrane perforations with ear drops containing basic fibroblast growth factor and epidermal growth factor, but these methods have been discontinued due to their high cost and poor efficacy. Another method involves applying traditional Chinese medicine film, but this is only suitable for small perforations with residual edges and is ineffective for large perforations. In my country, over 500,000 new cases of tympanic membrane perforation are diagnosed annually, of which approximately 150,000 are unable to undergo surgery due to economic constraints or contraindications. Therefore, a safe, efficient, and convenient non-surgical treatment option is urgently needed. Summary of the Invention

[0004] To address the aforementioned challenges, this invention provides a combined traditional Chinese and Western medicine drug for treating tympanic membrane perforation and its preparation method, enabling non-surgical repair of large tympanic membrane perforations and resolving the problems of large trauma, high cost, and numerous complications associated with traditional surgery. Furthermore, it provides a preparation method and standardized usage protocol for the drug to meet clinical treatment needs.

[0005] To achieve the above functions, the technical solution adopted by the present invention is as follows: A combination of traditional Chinese and Western medicine for treating tympanic membrane perforation, comprising traditional Chinese medicine components and Western medicine components, with a dosage per 1080 ml of preparation: Chinese herbal ingredients: safflower 6-30g, angelica 10-40g, frankincense 6-30g, myrrh 6-30g, chuanxiong 6-30g, and cattail pollen 10-20g; Western medicine component: α-chymotrypsin, the dosage is 4000U per 1 ml of mixture.

[0006] Preferably, the optimal weight ratio of the Chinese herbal components is: 12g safflower, 18g angelica sinensis, 12g frankincense, 12g myrrh, 12g chuanxiong rhizome, and 15g cattail pollen.

[0007] This invention also discloses a method for preparing a combination of traditional Chinese and Western medicine for treating tympanic membrane perforation, comprising the following steps: S1: Extraction of Chinese herbal medicine: Weigh the Chinese herbal medicine components according to the proportion, put them into a decoction pot, add 10 times the amount of water for the first decoction, and simmer over low heat for 2 hours; add 8 times the amount of water for the second decoction, and simmer over low heat for 1.5 hours; combine the two decoctions, filter with gauze to remove the dregs, and obtain crude extract. S2: Concentration and precipitation: Place the crude extract in a vacuum concentrator and concentrate it at 60℃ and 0.08MPa. After taking it out, let it stand at room temperature for 24-48 hours to allow the impurities to precipitate fully. S3: Formulation: Take the supernatant, first filter it with cotton to remove large particulate impurities, then filter it with a 0.45μm filter membrane to obtain a clear filtrate; adjust the pH of the filtrate to 7.2-7.9 with NaOH solution; S4: Add glycerol to the filtrate at a volume ratio of 2:3 (glycerol to filtrate), stir well, and then place in an autoclave at 121°C for 30 minutes. After sterilization, cool to room temperature, seal in 5ml dropper bottles to obtain the mother liquor of traditional Chinese medicine, and store in a cool, dry place. S5: Mixed use: Before use, take 1ml of the Chinese medicine mother liquor and inject it into an ampoule containing 4000U α-chymotrypsin. Shake to completely dissolve the enzyme powder and mix well to obtain the ear drops that can be used.

[0008] Preferably, the volume of the concentrated medicinal juice in step S2 is 300 ml.

[0009] The application of a combination of traditional Chinese and Western medicine for treating tympanic membrane perforation in the preparation of a treatment for tympanic membrane perforation, wherein the combination drug is administered via ear drops, specifically including the following operations: 1. Preparation before medication: Disinfect the external auditory canal with 75% alcohol and suction out any secretions from the external auditory canal; 2. Instillation procedure: With the affected ear facing upwards, instill 0.5-1 ml of the well-mixed ear drops into the affected ear each time, twice a day; 3. Treatment course management: A follow-up cycle is 14 days of continuous medication. If the perforation does not shrink, stop treatment; if the perforation shrinks, continue treatment. When the perforation shrinks to 3-4mm, stop ear drops and use a round thin paper to patch the perforation. There is no need to scrape the edges. 4. Total course of treatment: One course of treatment consists of two consecutive months of ear drops. A maximum of two courses of treatment are required. Follow-up is required for three months to two years after the course of treatment.

[0010] The beneficial effects achieved by adopting the above structure in this invention are as follows: Selection and effects of Chinese herbal components: Safflower invigorates blood circulation, removes blood stasis, relieves pain, and improves local blood circulation, providing a blood supply guarantee for tympanic membrane repair; Angelica sinensis nourishes and invigorates blood, regulates menstruation, relieves pain, and promotes tissue repair and regeneration; Frankincense invigorates blood circulation, promotes qi circulation, relieves pain, and promotes tissue regeneration, enhancing the growth capacity of the tympanic membrane fibrous layer; Myrrh invigorates blood circulation, relieves pain, reduces swelling, and promotes tissue regeneration, working synergistically with Frankincense to enhance the tissue regeneration effect; Ligusticum chuanxiong invigorates blood circulation, promotes qi circulation, dispels wind, relieves pain, improves microcirculation, and promotes drug absorption; Typha pollen stops bleeding, removes blood stasis, promotes urination, assists in improving local blood circulation, and reduces inflammatory response.

[0011] Selection and action of Western medicine components: α-chymotrypsin can decompose necrotic tissue and scar tissue, loosen adhesions, disrupt abnormal healing of epithelium and mucosa, and create conditions for the growth of fibrous layer.

[0012] The effective dosage range of each component was determined through extensive pre-clinical trials to ensure therapeutic efficacy while avoiding adverse reactions. Safflower 6-30g: Less than 6g is insufficient to promote blood circulation and remove blood stasis, while more than 30g may cause local irritation; Angelica sinensis 10-40g: 10g is the minimum effective dose, and 40g is the maximum safe dose. Overdose may cause dizziness. Frankincense and myrrh, 6-30g each: work synergistically to promote tissue regeneration; if the dosage is too low, the tissue regeneration effect will be insignificant. Chuanxiong 6-30g: Regulates local blood circulation; dosage range is matched with safflower. 10-20g of Typha pollen: It has both blood-activating and anti-inflammatory effects, and the effect is stable within the range of 10-20g. α-Chymotrypsin 4000U / ml: This concentration can effectively loosen adhesions without damaging the tympanic membrane tissue. It disrupts the abnormal healing of the epithelium and mucosa at the perforation edge, allowing the sealed fibrous layer to be exposed and grow, ultimately achieving self-healing of the tympanic membrane. Attached Figure Description

[0013] Figure 1 This invention relates to a case study of the repair process of a combined traditional Chinese and Western medicine drug for treating tympanic membrane perforation and its preparation method. Figure 1 ; Figure 2 This invention relates to a case study of the repair process of a combined traditional Chinese and Western medicine drug for treating tympanic membrane perforation and its preparation method. Figure 2 ; Figure 3 This invention relates to a case study of the repair process of a combined traditional Chinese and Western medicine drug for treating tympanic membrane perforation and its preparation method. Figure 3 . Detailed Implementation

[0014] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0015] S1: Extraction of Chinese herbal medicine: 12g safflower, 18g angelica sinensis, 12g frankincense, 12g myrrh, 12g chuanxiong rhizome, 15g cattail pollen, and lyophilized α-chymotrypsin powder (4000U / vial) are placed in a decoction pot. For the first decoction, add 600ml of water and simmer over low heat for 2 hours. For the second decoction, add 480ml of water and simmer over low heat for 1.5 hours. Combine the two decoctions, filter, and concentrate under reduced pressure to 300ml. S2: Concentration and precipitation: The crude extract is placed in a vacuum concentrator and concentrated at 60°C and 0.08MPa. After being removed, it is left at room temperature for 24 hours to allow impurities to precipitate fully. S3: Formulation: Take the supernatant, first filter it with cotton to remove large particulate impurities, then filter it with a 0.45μm filter membrane to obtain a clear filtrate; adjust the pH of the filtrate to 7.7 with NaOH solution; S4: Add 200ml of glycerin and mix well. Place the mixture in an autoclave and sterilize at 121℃ for 30 minutes. After sterilization, cool to room temperature and seal in a 5ml dropper bottle to obtain the mother liquor of traditional Chinese medicine. Store in a cool and dry place. S5: Mixed use: Before use, take 1ml of Chinese medicine mother liquor and 1 vial of 4000U α-chymotrypsin and mix to dissolve. Shake to completely dissolve the enzyme powder and mix evenly to obtain the ear drops that can be used.

[0016] S1: Extraction of Chinese herbal medicine: 6g safflower, 10g angelica sinensis, 6g frankincense, 6g myrrh, 6g chuanxiong rhizome, 10g cattail pollen, and lyophilized α-chymotrypsin powder (4000U / vial) are placed in a decoction pot. For the first decoction, add 300ml of water and simmer over low heat for 2 hours. For the second decoction, add 240ml of water and simmer over low heat for 1.5 hours. Combine the two decoctions, filter, and concentrate under reduced pressure to 150ml. S2: Concentration and precipitation: The crude extract is placed in a vacuum concentrator and concentrated at 60°C and 0.08 MPa. After being removed, it is left at room temperature for 36 hours to allow impurities to precipitate fully. S3: Formulation: Take the supernatant, first filter it with cotton to remove large particulate impurities, then filter it with a 0.45μm filter membrane to obtain a clear filtrate; adjust the pH of the filtrate to 7.2 with NaOH solution; S4: Add 100ml of glycerin and mix well. Place the mixture in an autoclave and sterilize at 121℃ for 30 minutes. After sterilization, cool to room temperature and seal in a 5ml dropper bottle to obtain the mother liquor of traditional Chinese medicine. Store in a cool and dry place. S5: Mixed use: Before use, take 1ml of Chinese medicine mother liquor and 1 vial of 4000U α-chymotrypsin and mix to dissolve. Shake to completely dissolve the enzyme powder and mix evenly to obtain the ear drops that can be used.

[0017] S1: Extraction of Chinese herbal medicine: 30g safflower, 40g angelica sinensis, 30g frankincense, 30g myrrh, 30g chuanxiong rhizome, 20g cattail pollen, and lyophilized α-chymotrypsin powder (4000U / vial) are placed in a decoction pot. For the first decoction, add 900ml of water and simmer over low heat for 2 hours. For the second decoction, add 720ml of water and simmer over low heat for 1.5 hours. Combine the two decoctions, filter, and concentrate under reduced pressure to 450ml. S2: Concentration and precipitation: The crude extract is placed in a vacuum concentrator and concentrated at 60°C and 0.08MPa. After being removed, it is left at room temperature for 48 hours to allow impurities to precipitate fully. S3: Formulation: Take the supernatant, first filter it with cotton to remove large particulate impurities, then filter it with a 0.45μm filter membrane to obtain a clear filtrate; adjust the pH of the filtrate to 7.5 with NaOH solution; S4: Add 300ml of glycerin and mix well. Place the mixture in an autoclave and sterilize at 121℃ for 30 minutes. After sterilization, cool to room temperature and seal in a 5ml dropper bottle to obtain the mother liquor of traditional Chinese medicine. Store in a cool and dry place. S5: Mixed use: Before use, take 1ml of Chinese medicine mother liquor and 1 vial of 4000U α-chymotrypsin and mix to dissolve. Shake to completely dissolve the enzyme powder and mix evenly to obtain the ear drops that can be used.

[0018] 1. Subjects: 12 outpatients (13 ears), 8 males (8 ears) and 4 females (5 ears); aged 17-62 years, with an average age of 48 years; disease duration 2-12 years, with an average of 8 years; all had total perforation of the pars tensa of the tympanic membrane due to chronic suppurative otitis media, which could not be repaired, and no cholesteatoma in the middle ear mastoid process.

[0019] 2. Treatment method: Use the drug described in Example 1, 1 ml once a day, for 14 days as one course of treatment. Follow up for 5-9 years after one course of treatment.

[0020] 3. Efficacy criteria: Significant effect: The tympanic membrane heals within 2 months after the instillation of the drops, and the air-bone difference in the audiometry is <10dB; Effective: The perforation shrinks within 2 months after the drops are applied, and the perforation can be healed by patching. The air-bone difference in the audiometry test is <10dB. Invalid: No change in puncture, no change or worse in audiometry.

[0021] 4. Experimental results: 4 cases (4 ears) showed significant improvement, 5 cases (5 ears) showed improvement, and 3 cases (4 ears) showed no improvement, with a total effective rate of 76.9%. The morphology and thickness of the newly grown tympanic membrane were normal, the hearing recovery was satisfactory, there was no recurrence during the follow-up period, and no adverse reactions were found.

[0022] 1. Subjects: 64 patients (64 ears) were randomly divided into a treatment group and a control group, with 32 patients in each group. The treatment group consisted of 10 males and 22 females; aged 22-67 years (mean 47.2 years); disease duration 3.5-52.0 years (mean 24.3 years); 26 patients did not undergo surgery, and 6 underwent failed surgical repair. The control group consisted of 15 males and 17 females; aged 21-72 years (mean 46.1 years); disease duration 2.5-54.0 years (mean 25.8 years); 29 patients did not undergo surgery, and 3 underwent failed surgical repair. There were no significant differences in patient data between the two groups, making them comparable.

[0023] 2. Treatment methods: The treatment group was treated with the drug described in Example 1 according to the method of use of the present invention; the control group was treated with sterile saline as a placebo, and the method of use was the same as that of the treatment group.

[0024] 3. Observation indicators: tympanic membrane healing status, hearing improvement (air-bone difference measured before treatment - air-bone difference measured after treatment), and adverse reactions.

[0025] 4. Experimental Results: Efficacy comparison: In the treatment group, 4 cases showed significant improvement, 11 cases showed improvement, and 17 cases showed no improvement, with a total effective rate of 46.9%; in the control group, all 32 cases showed no improvement. Among the 15 patients who healed in the treatment group, 2 healed within 2 months, 4 healed within 2-6 months, and 9 healed within 6-15 months; among the healed tympanic membranes, 11 had normal shape and thickness, 3 healed with scarring, and 1 healed with very thin tympanic membrane.

[0026] Hearing improvement: The hearing improvement in the treatment group was 14.4±6.1dB, while that in the control group was -0.1±7.6dB, and the difference between the two groups was statistically significant (P<0.05). The air-bone conductance difference in the healed patients in the treatment group was 4.5±4.1dB after treatment, which was significantly lower than before treatment.

[0027] Adverse reactions: Only 2 cases in the treatment group developed infections with purulent discharge from the middle ear cavity. The infections were controlled after one week of using levofloxacin ear drops after discontinuation of the drug. There were no other adverse reactions such as dizziness, facial paralysis, or hearing loss. In the patients who did not respond to the treatment, there were no abnormalities in the middle ear mucosa during subsequent surgical repair, and all of them achieved primary healing after surgery.

[0028] 1. Subjects: 20 patients with simple chronic suppurative otitis media and tympanic membrane perforation caused by trauma, with a disease course of ≥2 years.

[0029] 2. Treatment method: The combination of drugs of this invention is used, with 0.5ml of the drug being dropped into the ear twice a day for 14 days as one course of treatment.

[0030] 3. Experimental results: The effective rate was 80%. Of the 20 ears, 16 were completely healed, with normal tympanic membrane shape and thickness, satisfactory hearing recovery, and air-bone conduction difference <15dB. Treatment failed in 4 ears, of which 2 were successfully repaired by subsequent surgery without adverse reactions.

[0031] 1. Verification by multiple clinical data sets: Through three levels of clinical verification, including small-sample observation, randomized controlled trials, and expanded-sample trials, the drug has shown a stable therapeutic effect on tympanic membrane perforation, with a total effective rate of 46.9%-80%, significant improvement in hearing, and tympanic membrane morphology that is close to normal after healing.

[0032] 2. Long-term follow-up verification: The longest follow-up period was 9 years. No recurrence or hearing loss occurred in the healed patients, proving that the treatment effect was lasting and stable.

[0033] 3. Significant comparative advantages: Compared with traditional surgery, it has advantages such as less trauma, no surgical complications, and lower cost; compared with existing drug therapies, it has a wider range of applications, more stable efficacy, and lower price.

[0034] The present invention and its embodiments have been described above, and such description is not restrictive. In conclusion, if those skilled in the art are inspired by this description and design similar structures and embodiments without departing from the spirit of the invention, such designs should fall within the protection scope of the present invention.

Claims

1. A combined traditional Chinese and Western medicine drug for treating tympanic membrane perforation, comprising traditional Chinese medicine components and Western medicine components, characterized in that, Based on the dosage per 1080 ml of formulation: Chinese herbal ingredients: safflower 6-30g, angelica 10-40g, frankincense 6-30g, myrrh 6-30g, chuanxiong 6-30g, and cattail pollen 10-20g; Western medicine component: α-chymotrypsin, the dosage is 4000U per 1 ml of mixture.

2. The combined traditional Chinese and Western medicine treatment for tympanic membrane perforation according to claim 1, characterized in that, The optimal weight ratio of the Chinese herbal components is as follows: 12g safflower, 18g angelica sinensis, 12g frankincense, 12g myrrh, 12g chuanxiong rhizome, and 15g cattail pollen.

3. The method for preparing a combined traditional Chinese and Western medicine drug for treating tympanic membrane perforation according to claim 1, characterized in that, Includes the following steps: S1: Extraction of Chinese herbal medicine: Weigh the Chinese herbal medicine components according to the proportion, put them into a decoction pot, add 10 times the amount of water for the first decoction, and simmer over low heat for 2 hours; add 8 times the amount of water for the second decoction, and simmer over low heat for 1.5 hours; combine the two decoctions, filter with gauze to remove the dregs, and obtain crude extract. S2: Concentration and precipitation: Place the crude extract in a vacuum concentrator and concentrate it at 60℃ and 0.08MPa. After taking it out, let it stand at room temperature for 24-48 hours to allow the impurities to precipitate fully. S3: Formulation: Take the supernatant, first filter it with cotton to remove large particulate impurities, then filter it with a 0.45μm filter membrane to obtain a clear filtrate; adjust the pH of the filtrate to 7.2-7.9 with NaOH solution; S4: Add glycerol to the filtrate at a volume ratio of 2:3 (glycerol to filtrate), stir well, and then place in an autoclave at 121°C for 30 minutes. After sterilization, cool to room temperature, seal in 5ml dropper bottles to obtain the mother liquor of traditional Chinese medicine, and store in a cool, dry place. S5: Mixed use: Before use, take 1ml of the Chinese medicine mother liquor and inject it into an ampoule containing 4000U α-chymotrypsin. Shake to completely dissolve the enzyme powder and mix well to obtain the ear drops that can be used.

4. The method for preparing a combined traditional Chinese and Western medicine drug for treating tympanic membrane perforation according to claim 3, characterized in that, In step S2, the volume of the concentrated medicinal juice is 300 ml.

5. The application of the combined traditional Chinese and Western medicine drug for treating tympanic membrane perforation as described in any one of claims 1-4 in the preparation of a drug for treating tympanic membrane perforation, characterized in that, The combined medication is administered via ear drops, specifically including the following procedures:

1. Preparation before medication: Disinfect the external auditory canal with 75% alcohol and suction out any secretions from the external auditory canal; 2. Instillation procedure: With the affected ear facing upwards, instill 0.5-1 ml of the well-mixed ear drops into the affected ear each time, twice a day; 3. Treatment course management: A follow-up cycle is 14 days of continuous medication. If the perforation does not shrink, stop treatment; if the perforation shrinks, continue treatment. When the perforation shrinks to 3-4mm, stop ear drops and use a round thin paper to patch the perforation. There is no need to scrape the edges.

4. Total course of treatment: One course of treatment consists of two consecutive months of ear drops. A maximum of two courses of treatment are required. Follow-up is required for three months to two years after the course of treatment.

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